Early discussions of this compound have revolved around whether it possesses an appreciable affinity for the μ-opioidreceptor given its structural relationship to 3-HO-PCP, which has been shown to display affinity for the μ-opioidreceptor in animal models.[2] Whether it produces any of its theorized opioid effects in humans is the subject of ongoing discussion. If it does, 3-HO-PCE may pose unique risks relative to other dissociatives, particularly when it is redosed.

There is a lack of data of the pharmacological properties, metabolism and toxicity of 3-HO-PCE. To date, there have been no analytical studies conducted on samples of 3-HO-PCE distributed through the grey market via independent laboratories.[1] Due to an unknown toxicity profile and likely similar habit-forming properties shared by other hydroxylanated arylcyclohexylamines, it is strongly recommended that one use proper harm reduction practices if choosing to use this substance.

History and culture

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On October 18, 2012 the Advisory Council on the Misuse of Drugs in the United Kingdom released a report about methoxetamine, saying that the "harms of methoxetamine are commensurate with Class B of the Misuse of Drugs Act (1971)", despite the fact that the act does not classify drugs based on harm. The report went on to suggest that all analogues of MXE should also become class B drugs and suggested a catch-all clause covering both existing and unresearched arylcyclohexamines, which includes 3-HO-PCE.[3]

Chemistry

3-HO-PCE, or 3-hydroxyeticyclidine, is a synthetic dissociative of the arylcyclohexylamine class. The structure of 3-HO-PCE is comprised of cyclohexane, a six-member saturated ring, bonded to two additional groups at R1. One of these an ethyl chain bonded at its nitrogen group. The other ring is an aromatic phenyl ring, substituted at R3 with a hydroxy group.

3-HO-PCE is an analog of PCE and structurally homologous to 3-MeO-PCE.

Pharmacology

The NMDA (N-Methyl-D-Aspartate) receptor, a specific subtype of glutamate receptor, modulates the transmission of electrical signals between neurons in the brain and spinal cord; for the signals to pass, the receptor must be open.

There is ongoing speculation as to whether this compound possesses μ-opioid receptor activity due to its structural relationship to 3-HO-PCP, which has been found to have appreciable affinity as a μ-opioidreceptoragonist in animal models.[2]

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWikicontributors. These effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects

The physical effects of this substance have been reported to be relatively unpronounced or difficult to detect.

Seizure - This extent to which this effect can be produced is unknown but can likely happen in those predisposed to them, especially while in physically taxing conditions such as being dehydrated, undernourished, overheated, or fatigued.

The disconnective effects of this compound appear to be less prominent compared to dissociatives like ketamine or MXE. They seem to not occur at common doses and may only occur at levels that may be accompanied by potentially dangerous side effects.

Cognitive effects

Compulsive redosing - This effect is more prominent based on the route of administration used. For example, it is especially present when smoked or vaporized, due to the relative abruptness of the substance entering and leaving the bloodstream.

Auditory effects

Visual effects

Visual acuity suppression - While lower doses of this compound may produce mild visual acuity enhancements, this effect quickly disappears as one's general visual faculties become suppressed as the dose is increase.

The toxicity and long-term health effects of recreational 3-HO-PCE use has not been studied in any scientific context and the exact toxic dosage is unknown. This is because 3-HO-PCE has a very short history of human usage.

Tolerance and addiction potential

Early reports have characterized the chronic use of 3-HO-PCE as moderately addictive with a moderate potential for adverse side effects such as psychosis. In comparison to other dissociatives, 3-HO-PCE has been reported to be more potentially habit-forming than MXE, diphenidine, ephenidine, DCK, and ketamine. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.

Tolerance to many of the effects of 3-HO-PCE are expected to develop with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 4 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). 3-HO-PCE presents cross-tolerance with all dissociatives, meaning that after the consumption of 3-HO-PCE, all dissociatives will have a reduced effect.

It is strongly recommended that one exercise extreme caution and harm reduction practices when using this substance.

Users should avoid taking the drug multiple days in a row or becoming dependent/addicted to it as this seems to be the main common factor in the observed incidences of severe adverse effects.

The recommended dosage range should not be exceeded as high doses can trigger these effects as well.

Users should start with extremely low doses and work their way up as slowly as possible. Volumetric liquid dosing should preferably be used due to the substance's potency; most standard milligram scales cannot accurately weigh out doses below 10-15mg.[4]

Compulsive redosing before one has fully sobered up is not recommended and can result in too high of a dose, which can potentially produce serious adverse physical side effects.

Due to the risk of psychosis, it is not recommended to combine this drug with other substances, especially stimulants, psychedelics, or other dissociatives. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

Urinary tract effects

In terms of its long-term health effects when used repeatedly and excessively for extended periods of time, 3-HO-PCE is likely to exhibit similar bladder and urinary tract problems to those produced by ketamine, albeit to a lesser extent. This has been speculated to be due to the fact 3-HO-PCE is far more potent than ketamine so significantly less of material needs to be consumed. Symptoms of dissociative-induced cystitis can become extremely serious and can be described as:

Urinary frequency - Urinary frequency is the need to empty the bladder every few minutes.

Urinary urgency - This can be described as a sudden, compelling need to urinate.

Urinary pressure - This is experienced as a constant sensation of fullness in the bladder that is unrelieved by urination.

Pelvic and bladder pain - Pain can develop suddenly and severely, particularly as the bladder fills with urine.

Hematuria - This is visible blood in the urine.

Incontinence - This is the leakage of urine.

Dangerous interactions

Stimulants - Both stimulants and dissociatives carry the risk of adverse psychological reactions like anxiety, mania, delusions and psychosis and these risks are exacerbated when the two substances are combined.

Depressants - Because both depress the respiratory system, this combination can result in an increased risk of suddenly falling unconscious, vomiting and choking to death from the resulting suffocation. If nausea or vomiting occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.

Legal status

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United Kingdom: 3-HO-PCE is a class B drug in the UK and is illegal to possess, produce, supply, or import. As a derivative of 1-Phenylcyclohexylamine where the amine has been replaced with a 1-piperidyl group, further substituted in the phenyl ring with a hydroxy substituent, it is covered by the arylcyclohexylamine generic clause added to the Misuse of Drugs Act by S.I. 2013/239, which came into effect on the 26th February 2013.[5]